A new highly potent antagonist of bradykinin.
We report that the acylation of the N-terminus of [D-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin, one of the most potent bradykinin antagonists described to date, with 1-adamantane-acetic acid, results in an analogue with more than ten times enhanced potency. The new analogue does not increase the plasma catecholamines, even when administered at doses sufficient to inhibit by more than 90% the vasodepressor response to 250 ng of exogenous bradykinin. This modification suggests new possibilities for the design of even more potent and selective bradykinin antagonists for studying the physiopathology of bradykinin.
Lammek
B
B
Department of Medicine, Boston University School of Medicine, MA 02118.
Wang
Y X
YX
Gavras
I
I
Gavras
H
H
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D002395:Catecholamines; C053748:B 4162; D001920:Bradykinin